This cooperative vaccine development program will combine the resources and expertise of three separate institutions; Cambridge BioScience Corporation and the University of Massachusetts Medical Center which will serve as sites for individual projects and the E.G. and G. Mason Research Institute will participate in a subcontractor role. The long-term goal of the proposed program is to develop a single vaccine formulation that will be safe for human use and will prevent infection by HIV-2, the research described in this proposal will be used to generate actual preclinical data. We propose to test different recombinant produced HIV-2, env proteins, full-length glycosylated and nonglycosylated, as vaccine antigens using mice and standard immunological assays. We will also test the utility of three purified saponins as the adjuvants in mice and rhesus macaques and use these systems to identify and characterize the immune system components that are modulated by the adjuvants. Once the best saponin fractions have been identified, we will formulate experimental vaccines for testing in rhesus macaques. HIV-2 will infect rhesus macaques and in some instances induce disease symptoms. This property of HIV-2 will allow for detailed testing and challenge experiments in an animal model that is very similar to humans. However, this system is not yet well characterized so we have also proposed to characterize HIV-2 pathogenesis, primarily from an immunological viewpoint. This combination of projects has been organized to allow us to characterize multiple potential vaccine components and the test several vaccine formulation. The experience gained using HIV-2 will be applied to similar studies using HIV-1 towards the end of the proposed study period.